BeAT1D: Benign Autoimmunity and Type 1 Diabetes (BeAT1D)

National multi-center non-interventional case-control cohort study with collection of biological samples to characterize the autoimmune T and B lymphocytes involved in the development of type 1 diabetes.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: Biosampling

Detailed Description

The overall objective of this study is to define the differential characteristics of autoimmune T and B lymphocytes across individuals with T1D, other forms of diabetes or autoimmunity, and no disease. The hypothesis is that the characterization of the autoimmune T and B lymphocytes involved in T1D development may allow us to clarify the pathophysiological mechanisms of disease and to identify novel biomarkers for diagnostic, prognostic and therapeutic follow-up applications.

• Study Type: Observational
• Enrollment (Estimated): 1160

Contacts and Locations

• Study Contact: Name: Roberto Mallone, MD PhD; Phone Number: +33176535583; Email: roberto.mallone@inserm.fr
• Study Contact Backup: Name: Anna Jones; Email: anna.jones@inserm.fr

Study Locations

• France
  • Île-de-France Region
    • Bobigny, Île-de-France Region, France, 93000
      • Not yet recruiting
      • APHP Hopital Avicenne
      • Contact: Emmanuel Cosson, MD PhD
    • Bondy, Île-de-France Region, France, 93140
      • Not yet recruiting
      • APHP Hôpital J. Verdier
      • Contact: Nadine Lucidarme, MD
      • Sub-Investigator: Auriane Gibert, MD
    • Colombes, Île-de-France Region, France, 92700
      • Not yet recruiting
      • APHP Hôpital L. Mourier
      • Contact: Stéphanie Gréteau-Hamoumou, MD
    • Corbeil-Essonnes, Île-de-France Region, France, 91100
      • Not yet recruiting
      • Hôpital Sud Francilien
      • Contact: Alfred Penfornis, MD PhD
    • Le Chesnay, Île-de-France Region, France, 78150
      • Not yet recruiting
      • Hôpital Mignot - Service de Pédiatrie
      • Contact: Catherine Ajzenman, MD
    • Le Chesnay, Île-de-France Region, France, 78150
      • Not yet recruiting
      • Hôpital Mignot - Services de Diabétologie/Endocrinologie Adultes
      • Contact: Jean-Paul Beressi, MD
    • Le Kremlin-Bicêtre, Île-de-France Region, France, 94270
      • Not yet recruiting
      • APHP Hôpital Kremlin-Bicêtre
      • Contact: Cécile Petit-Bibal, MD
    • Paris, Île-de-France Region, France, 75010
      • Not yet recruiting
      • APHP Hôpital Lariboisière
      • Contact: Jean-François Gautier, MD PhD
      • Sub-Investigator: Jean-Pierre Riveline, MD PhD
    • Paris, Île-de-France Region, France, 75012
      • Not yet recruiting
      • APHP Hôpital Saint Antoine
      • Contact: Bruno Fève, MD PhD
    • Paris, Île-de-France Region, France, 75013
      • Not yet recruiting
      • APHP Hôpital Pitié-Salpêtrière - Service de Chirurgie
      • Contact: Sébastien Gaujoux, MD PhD
    • Paris, Île-de-France Region, France, 75013
      • Not yet recruiting
      • Hôpital Pitié-Salpêtrière - Service de Diabétologie
      • Contact: Chloé Amouyal, MD PhD
      • Sub-Investigator: Fabrizio Andreelli, MD PhD
    • Paris, Île-de-France Region, France, 75014
      • Not yet recruiting
      • APHP Hôpital Cochin - Service de Chirurgie
      • Contact: Pierre-Philippe Massault, MD
    • Paris, Île-de-France Region, France, 75014
      • Recruiting
      • APHP Hôpital Cochin - Service de Diabétologie et Immunologie Clinique
      • Contact: Etienne Larger, MD PhD
    • Paris, Île-de-France Region, France, 75015
      • Not yet recruiting
      • APHP Hôpital Européen G. Pompidou
      • Contact: Alina Radu, MD
    • Paris, Île-de-France Region, France, 75018
      • Not yet recruiting
      • APHP Hôpital Bichat
      • Contact: Ronan Roussel, MD PhD
    • Paris, Île-de-France Region, France, 75019
      • Not yet recruiting
      • APHP Hôpital R. Debré
      • Contact: Elise Bismuth, MD
    • Pontoise, Île-de-France Region, France, 95300
      • Not yet recruiting
      • Hôpital René Dubos
      • Contact: Catherine Campinos, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Participants with type 1 diabetes, other forms of diabetes or autoimmune endocrinopathies and participants undergoing surgical lymphadenectomy are recruited among patients referred to participating hospital centers.

Non-diabetic participants are recruited among patient's family members and via at-large calls for healthy volunteers.

Description

Inclusion Criteria:

1. Type 1 diabetes: type 1 diabetes, as defined by hyperglycemia and long-term insulin therapy started within 6 months from clinical onset; and/or the presence of at least one anti-islet auto-antibody.
2. Other forms of diabetes or autoimmune endocrinopathy: other forms of diabetes (e.g. type 2, ketosis-prone, familial, secondary, immunotherapy-induced diabetes); and/or other autoimmune endocrinopathies, isolated or multiple.
3. No diabetes: absence of diabetes or impaired glucose tolerance; absence of tumor, infectious or immune pathologies, or other conditions related to autoimmune or metabolic alterations that may bias the variables under study.
4. Lymphadenectomy planned in the frame of an abdominal surgery: pancreatic lymphadenectomy planned at the occasion of an abdominal surgery for the treatment of an underlying condition.

Exclusion Criteria:

For all participants: ongoing pregnancy; known HIV/HCV infection; absence of social security coverage; placement under judicial protection; absence of signature of the informed study consent.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Type 1 diabetes; As defined by the presence of hyperglycemia and/or islet auto-antibodies.	Other: Biosampling; Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy.
Other forms of diabetes or autoimmune endocrinopathy; Type 2 diabetes, ketosis-prone diabetes, familial diabetes, secondary diabetes, immunotherapy-induced diabetes; and/or autoimmune endocrinopathies.	Other: Biosampling; Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy.
No diabetes; No diabetes or impaired glucose tolerance; no cancer, infectious or immune pathologies; no other condition related to autoimmune and metabolic alterations that may bias the variables under study.	Other: Biosampling; Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy.
Lymphadenectomy planned at the occasion of an abdominal surgery; Patients undergoing a lymphadenectomy during surgery for the treatment of their underlying pathology.	Other: Biosampling; Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define the frequency and phenotype of autoimmune T lymphocytes reactive to islet antigens in the different study groups.	As measured by flow cytometry and sequencing techniques, with a sample size sufficient to attain a 92% statistical power and 5% alpha risk. Frequency will be expressed as number of antigen-reactive T lymphocytes per 100,000 total T lymphocytes (e.g. 20/100,000 or 0.02%). Phenotype will be expressed as percent of antigen-reactive T lymphocytes expressing a given phenotype, e.g. 20% naïve (CD45RA+CCR7+). These 2 measures will be aggregated by expressing the frequency of antigen-reactive T lymphocytes per 100,000 total T lymphocytes expressing a given phenotype, e.g. 20/100,000 antigen-reactive T lymphocytes with 20% naïve will be expressed as 4/100,000 naive antigen-reactive T lymphocytes.	6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define the frequency and phenotype of autoimmune B lymphocytes reactive to islet antigens in the different study groups.	As measured by flow cytometry and sequencing techniques, with a sample size sufficient to attain a 92% statistical power and 5% alpha risk. Frequency will be expressed as number of antigen-reactive B lymphocytes per 100,000 total B lymphocytes (e.g. 20/100,000 or 0.02%). Phenotype will be expressed as percent of antigen-reactive B lymphocytes expressing a given phenotype, e.g. 20% memory (CD24+CD38-negative). These 2 measures will be aggregated by expressing the frequency of antigen-reactive B lymphocytes per 100,000 total B lymphocytes expressing a given phenotype, e.g. 20/100,000 antigen-reactive B lymphocytes with 20% memory will be expressed as 4/100,000 memory antigen-reactive B lymphocytes.	6 years
To identify novel islet epitopes recognized by autoimmune T and B lymphocytes.	As measured by a lymphocyte frequency within the expected range, e.g. 1-50/million.	6 years
To define the phenotype of these lymphocytes.	As defined by exploratory analyses based on omics techniques.	6 years
To define the pathogenicity of these lymphocytes against pancreatic beta cells.	As measured by an in vitro killing of beta-cell targets significantly (e.g. >2-fold) higher than the killing observed with control lymphocytes.	6 years
To define the antigen receptors used by these lymphocytes to recognize their target epitopes.	As defined by sequencing techniques and sequence annotation using IMGT and MiXCR. Sequence sharing and similarities across receptors will be measured using MiXCR and stringdist.	6 years
To define the correlation between the biomarkers analyzed and insulin secretion.	As measured based on the correlation with fasting C-peptide levels >0.2 nM.	6 years
To define the differences between lymphocytes in the blood and those in pancreatic lymph nodes.	As measured using the previous frequency and phenotype readouts.	6 years

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Roberto Mallone, MD PhD, INSERM U1016 Cochin Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2022
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: October 29, 2021
• First Submitted That Met QC Criteria: November 18, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Type 1 diabetes; Biomarkers; Autoimmunity; Lymphocytes; Beta cells
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1; Autoimmune Diseases
• Other Study ID Numbers: C20-61; 2021-A01619-32 (Other Identifier: ID RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No